Reversible and irreversible tumor progression of a weakly malignant rat mammary carcinoma cell line by in vitro exposure to epidermal growth factor.
We examined the effects of epidermal growth factor (EGF) on tumor progression of a weakly malignant rat mammary carcinoma cell line, ER-1. In vitro treatment with EGF enhanced tumorigenicity, metastatic capacity and in vitro invasive capacity of ER-1 cells. The increased malignancy of ER-1 cells was reversible, when the cells were pretreated with EGF for 24 h, whereas it was irreversible when pretreated with EGF for 1 month. EGF treatment elevated the intracellular peroxide level in ER-1 cells. When ER-1 cells were treated with EGF in the presence of N-acetylcysteine, a chemical antioxidant, the reversible or irreversible EGF-induced progression was inhibited. These results suggest that the reversible or irreversible tumor progression in ER-1 cells occur in accordance with the duration of exposure to EGF, and that reactive oxygen species may be involved in the progression.
Nagayasu
H
H
Division of Pathology, Cancer Institute, Hokkaido University, School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060, Japan.
Hamada
J
J
Nakata
D
D
Shibata
T
T
Kobayashi
M
M
Hosokawa
M
M
Takeichi
N
N
D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D004249:DNA Damage / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017931:DNA Primers; D016166:Free Radical Scavengers; D010545:Peroxides; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000111:Acetylcysteine